Download Figure 4-1 General structural formula for α

Voet Biochemistry 3e Page 65
© 2004 John Wiley & Sons, Inc.
Figure 4-1
General structural formula for α-amino acids.
Voet Biochemistry 3e Page 65
© 2004 John Wiley & Sons, Inc.
Figure 4-2
Zwitterionic form of the α-amino acids that
occur at physiological pH values.
Voet Biochemistry 3e Page 68
© 2004 John Wiley & Sons, Inc.
Figure 4-3
dipeptide.
Condensation of two α-amino acids to form a
Voet Biochemistry 3e Page 69
© 2004 John Wiley & Sons, Inc.
Figure 4-4a
form.
Structure of phenylalanine. (a) Ball and stick
Voet Biochemistry 3e Page 69
© 2004 John Wiley & Sons, Inc.
Figure 4-4b
model.
Structure of phenylalanine. (b) Space-filling
Voet Biochemistry 3e Page 69
© 2004 John Wiley & Sons, Inc.
Figure 4-5
Structure of cystine.
Voet Biochemistry 3e Page 71
© 2004 John Wiley & Sons, Inc.
Figure 4-8
The tetrapeptide Ala-Tyr-Asp-Gly.
Voet Biochemistry 3e Page 71
© 2004 John Wiley & Sons, Inc.
Figure 4-9
Greek lettering scheme used to identify the
atoms in the glutamyl and lysyl R groups.
Voet Biochemistry 3e Page 220
© 2004 John Wiley & Sons, Inc.
Vast Majority
Figure 8-1
The trans-peptide group.
Voet Biochemistry 3e Page 220
© 2004 John Wiley & Sons, Inc.
Highly Un-favored
Figure 8-2
The cis-peptide group.
Voet Biochemistry 3e Page 220
© 2004 John Wiley & Sons, Inc.
Figure 8-3
A polypeptide chain in its fully extended
conformation showing the planarity of each of its peptide
groups.
Voet Biochemistry 3e Page 221
© 2004 John Wiley & Sons, Inc.
Figure 8-4
unit.
The torsional degrees of freedom in a peptide
Voet Biochemistry 3e Page 221
© 2004 John Wiley & Sons, Inc.
Steric Clash
Figure 8-5
Conformations of ethane.
Voet Biochemistry 3e
© 2004 John Wiley & Sons, Inc.
How would the energetic barrier vary
if the side chains were changed to
something other than hydrogen?
amide hydrogen
Voet Biochemistry 3e Page 221
© 2004 John Wiley & Sons, Inc.
carbonyl oxygen
The two angles are -60 deg (phi) and 30 deg (psi)
Figure 8-6
Steric interference between adjacent residues.
Voet Biochemistry 3e
© 2004 John Wiley & Sons, Inc.
Conformation Map or
Ramachandran diagram
A plot of the phi and psi angles
that are allowed based on the van
der Waals radii chosein
~75% of the angles are
not allowed
Pleated sheets
Voet Biochemistry 3e Page 222
© 2004 John Wiley & Sons, Inc.
Some helices
Figure 8-7
The Ramachandran diagram.
Voet Biochemistry 3e Page 222
© 2004 John Wiley & Sons, Inc.
Obtained from
high resolution
crystal structures
Figure 8-8
Conformation angles in proteins.
Outer limit
Voet Biochemistry 3e Page 223
© 2004 John Wiley & Sons, Inc.
Normally
allowed
Figure 8-9
The Ramachandran diagram of Gly residues
in a polypeptide chain.
Voet Biochemistry 3e
© 2004 John Wiley & Sons, Inc.
What does this say about glycine
as a side chain in proteins?
Voet Biochemistry 3e Page 223
© 2004 John Wiley & Sons, Inc.
P = pitch; N = number of repeating units per turn
Figure 8-10
Examples of helices.
ribbon
Voet Biochemistry 3e Page 224
© 2004 John Wiley & Sons, Inc.
Notice the “glue”
that holds this
structure together
Figure 8-11
The right-handed α helix.
Characteristics
Phi = -57 deg
Psi = -47 deg
N = 3/6 res/turn
Pitch = 5.4 A
Voet Biochemistry 3e Page 224
© 2004 John Wiley & Sons, Inc.
Which atoms form the
hydrogen bonds depicted in
this figure?
Figure 8-11
The right-handed α helix.
Voet Biochemistry 3e Page 225
© 2004 John Wiley & Sons, Inc.
Figure 8-12 Stereo, space-filling representation of an α
helical segment of sperm whale myoglobin (its E. helix) as
determined by X-ray crystal structure analysis.
Voet Biochemistry 3e
© 2004 John Wiley & Sons, Inc.
The alpha helix
• A common secondary structure in
both fibrous and globular protein
• Average length in globular protein is
~12 residues – a length of 18 A
• Helicases as long as 53 residues have
been observed
Voet Biochemistry 3e
© 2004 John Wiley & Sons, Inc.
Protein helical nomenclature
• Two numbers are involved
• The first number is the number of
residues per helical turn (n)
• The second number is the number of
atoms, including H, in the ring that is
closed by the hydrogen bond (m)
• In the case of the alpha helix it would be
called 3.613 helix
Voet Biochemistry 3e Page 225
© 2004 John Wiley & Sons, Inc.
Figure 8-13 The hydrogen bonding pattern of several
polypeptide helices.
Voet Biochemistry 3e Page 226
© 2004 John Wiley & Sons, Inc.
Figure 8-14 Comparison of the two polypeptide helices
that occasionally occur in proteins with the commonly
occurring α helix.
Voet Biochemistry 3e Page 227
© 2004 John Wiley & Sons, Inc.
Figure 8-15
The polyproline II helix.
Voet Biochemistry 3e Page 227
© 2004 John Wiley & Sons, Inc.
Figure 8-16a β pleated sheets. (a) The antiparallel β
pleated sheets.
Voet Biochemistry 3e Page 227
© 2004 John Wiley & Sons, Inc.
Figure 8-16b β pleated sheets. (b) The parallel β pleated
sheets.
Hydrogen bonding
Voet Biochemistry 3e Page 228
© 2004 John Wiley & Sons, Inc.
Alternating sides
for side chains
Figure 8-17 A two-stranded β antiparallel pleated sheet
drawn to emphasize its pleated appearance.
Voet Biochemistry 3e
© 2004 John Wiley & Sons, Inc.
Properties of beta sheets
• Beta sheets are common structural
motifs in proteins
• In globular protein they are 2-15
strands in size, 6 being the average
size
• Have an aggregate width of ~25 A
• Parallel beta sheets of <5 are rare
Voet Biochemistry 3e Page 228
© 2004 John Wiley & Sons, Inc.
Figure 8-18 Stereo, space-filling representation of the 6stranded antiparallel β pleated sheet in jack bean
concanavalin A as determined by crystal X-ray analysis.
Voet Biochemistry 3e Page 229
© 2004 John Wiley & Sons, Inc.
Figure 8-19a Polypeptide chain folding in proteins
illustrating the right-handed twist of β sheets. (a) Bovine
carboxypeptidase A.
Voet Biochemistry 3e Page 229
© 2004 John Wiley & Sons, Inc.
Example of a beta barrel – cylindrical structure
Figure 8-19b Polypeptide chain folding in proteins
illustrating the right-handed twist of β sheets. (b) Chicken
muscle triose phosphate isomerase.
Voet Biochemistry 3e Page 229
© 2004 John Wiley & Sons, Inc.
Figure 8-20 Connections between adjacent polypeptide
strands in β pleated sheets.
Voet Biochemistry 3e Page 230
© 2004 John Wiley & Sons, Inc.
Preferred right hand twisting of beta sheet
favors right handed crossover
Figure 8-21
Origin of a right-handed crossover connection.
Voet Biochemistry 3e
© 2004 John Wiley & Sons, Inc.
Around half of globular protein
structure is alpha helices and
beta sheets
The other half is mostly coil or
loop formation
Voet Biochemistry 3e Page 230
© 2004 John Wiley & Sons, Inc.
Linkage between residues 2 and 3 is flipped
Figure 8-22
Reverse turns in polypeptide chains.
Voet Biochemistry 3e
© 2004 John Wiley & Sons, Inc.
Coiled-coil structure although
irregular is not random coil
Voet Biochemistry 3e
© 2004 John Wiley & Sons, Inc.
Fibrous proteins have highly
elongated structures with secondary
structure being the dominating feature
Structure not well resolved by X-ray
crystallography
keratin
Voet Biochemistry 3e Page 233
© 2004 John Wiley & Sons, Inc.
Nonpolar
residues
Figure 8-27a The two-stranded coiled coil. (a) View down
the coil axis showing the interactions between the nonpolar
edges of the α helices.
keratin
Voet Biochemistry 3e Page 233
© 2004 John Wiley & Sons, Inc.
Red – hydrophobic strip
Figure 8-27b The two-stranded coiled coil. (b) Side view in
which the polypeptide back bone is represented by skeletal
(left) and space-filling (right) forms.
Voet Biochemistry 3e
© 2004 John Wiley & Sons, Inc.
Collagen – component of
connective tissue
Has great tensile strength and is one
of the most abundant proteins in
vertebrates
Voet Biochemistry 3e Page 234
© 2004 John Wiley & Sons, Inc.
•~33 Gly, 15-30% Pro and Hyp (4-hydroxypropyl)
•Every 3rd residue is Gly for packing reasons
Figure 8-28 The amino acid sequence at the C-terminal
end of the triple helical region of the bovine α1(I) collagen
chain.
Voet Biochemistry 3e Page 235
© 2004 John Wiley & Sons, Inc.
Figure 8-29
The triple helix of collagen.
Voet Biochemistry 3e Page 236
© 2004 John Wiley & Sons, Inc.
Staggered
conformation
Figure 8-30c
X-Ray structure of the triple helical collagen model
peptide (Pro-Hyp-Gly)10 in which the fifth Gly is replaced by Ala. (c)
A schematic diagram.
Voet Biochemistry 3e Page 237
© 2004 John Wiley & Sons, Inc.
Fibrils are covalently cross-linked
Figure 8-31
skin.
Electron micrograph of collagen fibrils from
Voet Biochemistry 3e
© 2004 John Wiley & Sons, Inc.
Globular proteins – compact
more sphere-like structures
Enzymes generally are part of this
group of proteins, as well as
transport and receptor proteins
Voet Biochemistry 3e Page 240
© 2004 John Wiley & Sons, Inc.
Figure 8-35 X-Ray diffraction photograph of a single
crystal of sperm whale myoglobin.
Voet Biochemistry 3e Page 231
© 2004 John Wiley & Sons, Inc.
For comparison
Figure 8-24 X-Ray diffraction photograph of a fiber of
Bombyx mori silk.
Voet Biochemistry 3e Page 244
© 2004 John Wiley & Sons, Inc.
Figure 8-39a Representations of the X-ray structure of
sperm whale myoglobin. (a) The protein and its bound heme
are drawn in stick form.
Voet Biochemistry 3e Page 244
© 2004 John Wiley & Sons, Inc.
Figure 8-39b Representations of the X-ray structure of
sperm whale myoglobin. (b) A diagram in which the protein is
represented by its computer-generated Cα backbone.
Voet Biochemistry 3e Page 244
© 2004 John Wiley & Sons, Inc.
Figure 8-39c Representations of the X-ray structure of
sperm whale myoglobin. (c) A computer-generated cartoon
drawing in an orientation similar to that of Part b.
Voet Biochemistry 3e
© 2004 John Wiley & Sons, Inc.
Side Chain Location Varies
with Polarity
•Nonpolar residues occur generally in the
interior of a protein away from the the
aqueous solvent (Val, Leu, Ile, Met, Phe)
•Charges polar residues are on the
surface of the protein (Arg, His, Lys, Asp,
Glu)
•Uncharged polar groups are usually on
the surface, but can also be found in the
interior. (Ser, Thr, Asn, Gln, Tyr, Trp)
Voet Biochemistry 3e Page 247
© 2004 John Wiley & Sons, Inc.
Figure 8-43a The H helix of sperm whale myoglobin. (a) A
helical wheel representation in which the side chain positions
about the α helix are projected down the helix axis onto a plane.
exterior
interior
White –main
chain
Purple – polar
side chains
Voet Biochemistry 3e Page 247
© 2004 John Wiley & Sons, Inc.
Brown –
nonpolar side
chains
Figure 8-44 A space-filling model of an antiparallel β sheet
from concanavalin A.
Voet Biochemistry 3e Page 258
© 2004 John Wiley & Sons, Inc.
Figure 8-56
A GRASP diagram of human growth hormone.
Voet Biochemistry 3e
© 2004 John Wiley & Sons, Inc.
Elements of Protein Structure
•Primary Structure – amino acid
sequence of polypeptide chain
•Seconday Structure – examples such
as beta sheet and alpha helix
•Tertiary Structure – three dimensional
structure. Consists of various protein
domains
•Quaternary Structure – arrangement
of several subunits – example of
hemoglobin
Voet Biochemistry 3e Page 266
© 2004 John Wiley & Sons, Inc.
Figure 8-63
The quaternary structure of hemoglobin.
Voet Biochemistry 3e Page 256
© 2004 John Wiley & Sons, Inc.
Table 8-4 (top) Structural Bioinformatics Websites (URLs).
Voet Biochemistry 3e Page 256
© 2004 John Wiley & Sons, Inc.
Table 8-4 (middle)
(URLs).
Structural Bioinformatics Websites